Patterns of Care in Neoadjuvant Chemoradiotherapy for Node-Positive Esophageal Adenocarcinoma.
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ABSTRACT: Background
The aims of this study were to examine the factors associated with use of neoadjuvant chemoradiotherapy (NCR) for patients with locally advanced esophageal cancer and to evaluate the effect of NCR on survival.Methods
The 2004 to 2015 National Cancer Database was used to identify patients with cT1-4aN1-3M0 (stage II-IVA) esophageal adenocarcinoma who underwent esophagectomy. Patients were stratified by receipt of NCR. A multivariable logistic regression was performed to examine factors associated with NCR, and survival between the 2 groups was compared using a multivariable Cox model.Results
Of 8076 patients meeting the study criteria, 1616 (20%) did not receive NCR and 6460 (80%) did. In a multivariable regression, factors associated with receipt of NCR were a later year of diagnosis, treatment in a high-volume center, and clinical stage III disease. Factors associated with nonreceipt of NCR were increasing age, comorbidities, and treatment in a Middle Atlantic, South Central, or Pacific state. Receipt of trimodality therapy was associated with improved survival compared with other or no perioperative therapies (adjusted hazard ratio, 0.80; 95% confidence interval, 0.74-0.87).Conclusions
Numerous personal-, demographic-, and treatment center-related factors account for variability in NCR for clinically node-positive esophageal adenocarcinoma, although neoadjuvant therapy was associated with a survival benefit. Further efforts are needed to identify reasons for these differences and design interventions to provide more equitable care for patients with esophageal cancer.
SUBMITTER: Raman V
PROVIDER: S-EPMC7669693 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe impact of neoadjuvant chemoradiotherapy (nCRT) on early stage esophageal cancer is unknown. Here, we compared the outcomes after esophagectomy alone or nCRT plus surgery for clinically staged node-negative esophageal cancer.MethodsWe searched the Surveillance, Epidemiology, and End Results database for patients with clinically node-negative (cN0) esophageal cancer from 2004 to 2016 who underwent surgery alone or nCRT plus surgery. Propensity score matching and Cox regression analysis were used to identify covariates associated with overall survival and cancer-specific survival.ResultsA total of 1587 patients were retrospectively identified, of whom 49.8% (n = 791) received nCRT and 80.2% (n = 1273) were truly node-negative diseases. For the entire cohort, surgery alone was associated with a statistically significant but modest absolute increase in survival outcomes (P < 0.01). After matching, nCRT was associated with improved five-year overall survival for pT3-4N0 (localized) disease (59.6% vs. 37.7%; P < 0.001) and pathological node-positive disease (60.5% vs. 40.7%; P = 0.002). Cox multivariate regression analysis revealed that the addition of nCRT for truly node-negative patients with tumor length ≥ 3 cm, pT1-2N0 (early-staged) and localized disease were independent risk factors for survival than surgery alone (P < 0.01).ConclusionsCompared with surgery alone, patients with cN0 esophageal cancer with pathological node-positive or localized true node-negative disease gain a significant survival benefit from nCRT. However, nCRT plus surgery was associated with decreased survival for early-staged true node-negative patients. This finding may have significant implications on the use of neoadjuvant chemoradiation in patients with cN0 disease.
| S-EPMC7471040 | biostudies-literature
Project description:Esophageal adenocarcinoma (EAC) is a disease with dismal treatment outcomes. Response to neoadjuvant chemoradiation (CRT) varies greatly. Although the underlying mechanisms of CRT resistance are not identified, accumulating evidence indicates an important role for local antitumor immunity. To explore the immune microenvironment in relation to response to CRT we performed an in-depth analysis using multiplex immunohistochemistry, flow cytometry and mRNA expression analysis (NanoString) to generate a detailed map of the immunological landscape of pretreatment biopsies as well as peripheral blood mononuclear cells (PBMCs) of EAC patients. Response to CRT was assessed by Mandard's tumor regression grade (TRG), disease-free- and overall survival. Tumors with a complete pathological response (TRG 1) to neoadjuvant CRT had significantly higher tumor-infiltrating T cell levels compared to all other response groups (TRG 2-5). These T cells were also in closer proximity to tumor cells in complete responders compared to other response groups. Notably, immune profiles of near-complete responders (TRG 2) showed more resemblance to non-responders (TRG 3-5) than to complete responders. A high CD8:CD163 ratio in the tumor was associated with an improved disease-free survival. Gene expression analyses revealed that T cells in non-responders were Th2-skewed, while complete responders were enriched in cytotoxic immune cells. Finally, complete responders were enriched in circulating memory T cells. preexisting immune activation enhances the chance for a complete pathological response to neoadjuvant CRT. This information can potentially be used for future patient selection, but also fuels the development of immunomodulatory strategies to enhance CRT efficacy.
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Project description:BackgroundThere are limited data regarding optimal surveillance after curative resection for esophageal cancer. Once disease recurrence is diagnosed, the prognosis is poor. The purpose of this article was to characterize disease recurrence in patients with early esophageal adenocarcinoma.MethodsTwo hundred sixty patients were identified from a prospective institutional database with pathologic T1 and T2 node-negative disease therapy treated with curative esophagectomy alone for esophageal adenocarcinoma between 1995 and 2017. Competing risk analysis was used to analyze factors associated with recurrence.ResultsThe 5-year cumulative incidence of recurrence was 12%. Predictive factors for increased risk of recurrence included increasing tumor size, poor differentiation, and pathologic T2 disease (P < .05), whereas presence of Barrett's esophagus on pathology was protective. Recurrence within 2 years was 2.5%, 6.1%, and 12% for T1a, T1b, and T2 disease, respectively. At 5 years cumulative incidence of recurrence was 8.2%, 11.5% and 22.2%, respectively. Median overall survival after recurrence was 1.04 years (95% confidence interval, 0.7-2.4). There were 14 subclinical and 13 symptomatic recurrences; patients with symptomatic recurrence had a significantly shorter overall survival after recurrence occurred (0.31 vs 0.71 years, P = .018).ConclusionsAmong early node-negative patients with esophageal cancer undergoing curative resection, 5-year recurrence was 12%. Survival after recurrence was poor, and only a few patients had isolated locoregional recurrence at time of diagnosis, suggesting that scheduled surveillance may have an important role.
| S-EPMC6878144 | biostudies-literature
Project description:ImportanceWhile neoadjuvant chemoradiation for esophageal cancer improves oncologic outcomes for a broad group of patients with locally advanced and/or node-positive tumors, it is less clear which specific subset of patients derives most benefit in terms of overall survival (OS).ObjectiveTo determine whether neoadjuvant chemoradiation based on esophageal adenocarcinoma histology has similar oncologic outcomes for patients treated with surgery alone when stratified by clinical nodal status.Design, setting, and participantsA retrospective analysis using the American College of Surgeons National Cancer Database from 1998 to 2006. Patients with esophageal adenocarcinoma histology and clinical stage T1bN1-N3 or T2-T4aN-/+M0 were divided into 2 treatment groups: (1) neoadjuvant chemoradiation followed by surgery and (2) surgery alone. Subset analysis within each treatment group was performed for clinically node-negative patients (cN-) vs node-positive patients (cN+) in conjunction with pathological nodal status. A propensity score-adjusted analysis, which included patient demographics, comorbidity status, and clinical T stage, was also performed.Main outcome and measuresThe primary outcome was 3-year OS. Secondary outcomes included margin status, postoperative length of stay, unplanned readmission rate, and 30-day mortality.ResultsA total of 1309 patients were identified, of whom 539 received neoadjuvant chemoradiation followed by surgery and 770 received surgery alone. Of the 1309 patients, 41.2% (n = 539) received neoadjuvant chemoradiation and 47.2% (n = 618) were cN+. Median follow-up for the entire cohort was 73.3 months (interquartile range, 64.1-93.5 months). The 3-year OS was better for neoadjuvant chemoradiation followed by surgery compared with surgery alone (49% vs 38%, respectively; P < .001). Stratifying based on clinical nodal status, the propensity score-adjusted OS was significantly better for cN+ patients who received neoadjuvant chemoradiation (hazard ratio, 0.52; 95% CI, 0.42-0.66; P < .001). In contrast, there was no difference in OS for cN- patients based on treatment (hazard ratio, 0.84; 95% CI, 0.65-1.10; P = .22).Conclusions and relevancePatients with cN+ esophageal adenocarcinoma benefit significantly from neoadjuvant chemoradiation. However, patients with cN- tumors treated with neoadjuvant chemoradiation plus surgery do not derive a significant OS benefit compared with surgery alone. This finding may have significant implications on the use of neoadjuvant chemoradiation in patients with cN- disease.
| S-EPMC5340565 | biostudies-literature
Project description:Although it was controversial for treating locally advanced resectable esophageal squamous cell carcinoma (ESCC), neoadjuvant chemoradiotherapy (NACR) was more widely accepted rather than neoadjuvant chemotherapy (NAC) worldwide. With the development of paclitaxel, a high response rate to NAC was reported in many studies. Our hypothesis is that lots of patients could get a response from NAC alone and avoid unnecessary NACR. Those who had no response from NAC could still response from the followed radiotherapy. We attempted to circumvent the controversy over the use of NAC, NACR and made a combined version, NAC ± neoadjuvant radiotherapy (NAR).The retrospective study compared NAC ± NAR with NACR between June 30, 2015 and October 31, 2016. Sixty consecutive borderline resectable ESCC were included: thirty-one in NAC ± NAR group and 29 in NACR group. The toxicities, response rates, operative data, complications, length of stay, and overall survival (OS) rates were evaluated.The response rate to NAC ± NAR was 93.5%; to NACR was 86.2%. There was no grade 3-4 non-hematologic adverse events after NAC ± NAR, but three in the NACR group. Arrhythmias (6.5% vs. 37.9%, P=0.003), pneumonitis (25.8% vs. 51.7%, P=0.039) and anastomotic leakage (0% vs. 13.8%, P=0.049) were more likely in NACR group. Postoperative hospitalization stays were significantly prolonged in the NACR (9 vs. 16 d, P<0.001). A point estimate of the 2-year OS rate of the NAC ± NAR group was 84.0%, the NACR group 80.7% (P=0.410).Compared with NACR, the NAC ± NACR provided the same survival benefits but low post operation complication rate. In the future, it might be a choice for locally advanced ESCC.
| S-EPMC6129884 | biostudies-other
Project description:BackgroundWe hypothesized that the ratio of positive lymph nodes to total assessed lymph nodes (LNR) is an indicator of cancer burden in esophageal adenocarcinoma and may identify patients who may most benefit from AC.ObjectiveThe aim of this study was to discern whether there is a threshold LNR above which AC is associated with a survival benefit in this population.MethodsThe 2004-2015 National Cancer Database was queried for patients who underwent upfront, complete resection of pT1-4N1-3M0 esophageal adenocarcinoma. The primary outcome, overall survival, was examined using multivariable Cox proportional hazards models employing an interaction term between LNR and AC.ResultsA total of 1733 patients were included: 811 (47%) did not receive AC whereas 922 (53%) did. The median LNR was 20% (interquartile range 9-40). In a multivariable Cox model, the interaction term between LNR and receipt of AC was significant (P = 0.01). A plot of the interaction demonstrated that AC was associated with improved survival beyond a LNR of about 10%-12%. In a sensitivity analysis, the receipt of AC was not associated with improved survival in patients with LNR <12% (hazard ratio 1.02; 95% confidence interval 0.72-1.44) but was associated with improved survival in those with LNR ≥12% (hazard ratio 0.65; 95% confidence interval 0.50-0.79).ConclusionsIn this study of patients with upfront, complete resection of node-positive esophageal adenocarcinoma, AC was associated with improved survival for LNR ≥12%. LNR may be used as an adjunct in multidisciplinary decision-making about adjuvant therapies in this patient population.
| S-EPMC7790855 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:After esophagectomy, adjuvant chemotherapy (S?+?CT) and adjuvant chemoradiotherapy (S?+?CRT) can improve survival in patients with node-positive resectable esophageal cancer. However, we are not aware of any studies that directly compared these adjuvant treatments. This study aimed to compare S?+?CT and S?+?CRT for patients with esophageal cancer. MATERIALS AND METHODS:We retrospectively identified patients with node-positive esophageal squamous cell carcinoma who underwent S?+?CT or S?+?CRT at Sichuan Cancer Hospital during 2008-2017. The patients' characteristics were compared, as well as their overall survival (OS) and disease-free survival (DFS) outcomes. Propensity score matching was used to create balanced patient groups according to adjuvant treatment, and a Cox proportional hazards model was used to identify factors that predicted the survival outcomes. RESULTS:The 859 eligible patients underwent S?+?CRT (250 patients, 29.1%) or S?+?CT (609 patients, 70.9%). After propensity score matching (247 patients per group), the 5-year OS rates were 41.8% for S?+?CRT and 26.8% for S?+?CT (p?=?0.028), and the 5-year DFS rates were 37.2% for S?+?CRT and 25.5% for S?+?CT (p?=?0.012). Multivariate Cox regression analysis of the matched samples revealed that, relative to the S?+?CT group, the S?+?CRT group had better OS (hazard ratio: 0.71, 95% CI: 0.56-0.91; p?=?0.006) and DFS (hazard ratio: 0.70, 95% CI: 0.56-0.88; p?=?0.002). CONCLUSION:Among patients with node-positive resectable esophageal squamous cell carcinoma, S?+?CRT was associated with better OS than S?+?CT. A multicenter randomized clinical trial is warranted to confirm these findings.
| S-EPMC7245784 | biostudies-literature
Project description:PurposeApproximately 15% to 43% of esophageal adenocarcinomas (EACs) are human epidermal growth factor receptor 2 (HER2) positive. Because dual-agent HER2 blockade demonstrated a survival benefit in breast cancer, we conducted a phase II feasibility study of trastuzumab and pertuzumab added to neoadjuvant chemoradiotherapy (nCRT) in patients with EAC.Patients and methodsPatients with resectable HER2-positive EAC received standard nCRT with carboplatin and paclitaxel and 41.4 Gy of radiotherapy, with 4 mg/kg of trastuzumab on day 1, 2 mg/kg per week during weeks 2 to 6, and 6 mg/kg per week during weeks 7, 10, and 13 and 840 mg of pertuzumab every 3 weeks. The primary end point was feasibility, defined as ≥ 80% completion of treatment with both trastuzumab and pertuzumab. An exploratory comparison of survival with a propensity score-matched cohort receiving standard nCRT was performed, as were exploratory pharmacokinetic and biomarker analyses.ResultsOf the 40 enrolled patients (78% men; median age, 63 years), 33 (83%) completed treatment with trastuzumab and pertuzumab. No unexpected safety events were observed. R0 resection was achieved in all patients undergoing surgery, with pathologic complete response in 13 patients (34%). Three-year progression-free and overall survival (OS) were 57% and 71%, respectively (median follow-up, 32.1 months). Compared with the propensity score-matched cohort, a significantly longer OS was observed with HER2 blockade (hazard ratio, 0.58; 95% CI, 0.34 to 0.97). Results of pharmacokinetic analysis and activity on [18F]fluorodeoxyglucose positron emission tomography scans did not correlate with survival or pathologic response. Patients with HER2 3+ overexpression or growth factor receptor-bound protein 7 (Grb7) -positive tumors at baseline demonstrated significantly better survival (P = .007) or treatment response (P = .016), respectively.ConclusionAddition of trastuzumab and pertuzumab to nCRT in patients with HER2-positive EAC is feasible and demonstrates potentially promising activity compared with historical controls. HER2 3+ overexpression and Grb7 positivity are potentially predictive for survival and treatment response, respectively.
| S-EPMC7007286 | biostudies-literature
Project description:BackgroundTumor regression grade (TRG) after neoadjuvant therapy is reportedly predictive of prognosis in esophageal cancer patients, as lack of a response to neoadjuvant therapy is associated with a poor prognosis. However, there is little information available on the timing and pattern of recurrence after esophagectomy for thoracic esophageal squamous cell carcinoma (TESCC) that takes into consideration TRG after neoadjuvant chemoradiotherapy (NACRT). Here, in an effort to gain insight into a treatment strategy that improves the prognosis of NACRT non-responders, we evaluated the patterns and timing of recurrence in TESCC patients, taking into consideration TRG after NACRT.MethodsA total of 127 TESCC patients treated with NACRT and esophagectomy between 2009 and 2017 were enrolled in this observational cohort study. TRGs were assigned based on the proportion of residual tumor cells in the area (TRG1, ≥1/3 viable cancer cells; 2, < 1/3 viable cancer cells; 3, no viable cancer cells). We retrospectively investigated the timing and patterns of recurrence and the prognoses in TESCC patients, taking into consideration TRG after NACRT.ResultsThe 127 participating TESCC patients were categorized as TRG1 (42 patients, 33%), TRG2 (56 patients, 44%) or TRG3 (29 patients, 23%). The locoregional recurrence rate was higher in TRG1 (36.4%) patients than combined TRG2-3 (7.4%) patients. Patients with TRG3 had better prognoses, though a few TRG3 patients experienced distant recurrence. There were no significant differences in median time to first recurrence or OS among patients with locoregional or distant recurrence. There was a trend toward better OS in TRG2-3 patients with recurrence than TRG1 patients with recurrence, but the difference was not significant.ConclusionsNACRT non-responders (TRG1 patients) experienced higher locoregional recurrence rates and earlier recurrence with distant or locoregional metastasis. TRG appears to be useful for establishing a strategy for perioperative treatments to improve TESCC patient survival, especially among TRG1 patients. (303 words).
| S-EPMC8576899 | biostudies-literature
Project description:The efficacy of surgery alone for patients with locally advanced esophageal cancer (EC) is still unsatisfactory. Presently, induction therapy followed by surgery is the standard treatment. Preoperative chemotherapy (CT) and chemoradiation (CRT) are proven effective induction therapies; however, few sample studies have addressed these treatments, thus, their superiority remains uncertain. We performed a systemic review and meta analysis to test the hypothesis that induction CRT prior to surgery could improve survival compared with induction CT alone.A comprehensive search of PubMed and the Ovid database for relevant studies comparing EC patients undergoing resection after treatment with induction CT alone or induction CRT was conducted. Hazard ratios (HR) and 95% confidence intervals (95% CI) were extracted from these studies to provide pooled estimates of the effect of induction therapy on overall survival.Five studies met the criteria for analysis. Statistical analysis demonstrated a survival benefit of induction CRT compared with induction CT alone (HR0.73, 95% CI 0.61-0.89; P = 0.002). Further analysis showed that induction CRT perioperative mortality and complication rates were higher than for induction CT alone (HR 2.96, 95% CI 1.38-6.37; HR1.6, 95% CI 1.30-1.98; P = 0.01, respectively).Published evidence comparing the different efficacies of induction CT and induction CRT is sparse, with few samples of adenocarcinoma. This analysis supports the view that, compared with induction CT, induction CRT could achieve a long-term survival benefit in EC patients.
| S-EPMC4773296 | biostudies-other